scholarly journals Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitin–proteasome system

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Weiyi Zhang ◽  
Qian Che ◽  
Hongsheng Tan ◽  
Xin Qi ◽  
Jing Li ◽  
...  
Keyword(s):  
Hela Cells ◽  
Ubiquitin Proteasome System ◽  
Streptomyces Sp ◽  
Hpv E6 ◽  
Ubiquitin Proteasome ◽  
Marine Streptomyces

scholarly journals Docosahexaenoic acid induces the degradation of HPV E6/E7 oncoproteins by activating the ubiquitin–proteasome system

2014 ◽  
Vol 5 (11) ◽  
pp. e1524-e1524 ◽  
Author(s):  
K Jing ◽  
S Shin ◽  
S Jeong ◽  
S Kim ◽  
K-S Song ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Ubiquitin Proteasome System ◽  
Hpv E6 ◽  
Ubiquitin Proteasome

scholarly journals Regulation of Subtilase Cytotoxin-Induced Cell Death by an RNA-Dependent Protein Kinase-Like Endoplasmic Reticulum Kinase-Dependent Proteasome Pathway in HeLa Cells

2012 ◽  
Vol 80 (5) ◽  
pp. 1803-1814 ◽  
Author(s):  
Kinnosuke Yahiro ◽  
Hiroyasu Tsutsuki ◽  
Kohei Ogura ◽  
Sayaka Nagasawa ◽  
Joel Moss ◽  
...  
Keyword(s):  
Er Stress ◽  
Hela Cells ◽  
Ubiquitin Proteasome System ◽  
Early Event ◽  
Caspase Activation ◽  
Ubiquitinated Proteins ◽  
Ubiquitin Proteasome ◽  
Dependent Protein ◽  
Activating Transcription Factor ◽  
Subtilase Cytotoxin

ABSTRACTShiga-toxigenicEscherichia coli(STEC) produces subtilase cytotoxin (SubAB), which cleaves the molecular chaperone BiP in the endoplasmic reticulum (ER), leading to an ER stress response and then activation of apoptotic signaling pathways. Here, we show that an early event in SubAB-induced apoptosis in HeLa cells is mediated by RNA-dependent protein kinase (PKR)-like ER kinase (PERK), not activating transcription factor 6 (ATF6) or inositol-requiring enzyme 1(Ire1), two other ER stress sensors. PERK knockdown suppressed SubAB-induced eIF2α phosphorylation, activating transcription factor 4 (ATF4) expression, caspase activation, and cytotoxicity. Knockdown of eIF2α by small interfering RNA (siRNA) or inhibition of eIF2α dephosphorylation by Sal003 enhanced SubAB-induced caspase activation. Treatment with proteasome inhibitors (i.e., MG132 and lactacystin), but not a general caspase inhibitor (Z-VAD) or a lysosome inhibitor (chloroquine), suppressed SubAB-induced caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage, suggesting that the ubiquitin-proteasome system controls events leading to caspase activation, i.e., Bax/Bak conformational changes, followed by cytochromecrelease from mitochondria. Levels of ubiquitinated proteins in HeLa cells were significantly decreased by SubAB treatment. Further, in an early event, some antiapoptotic proteins, which normally turn over rapidly, have their synthesis inhibited, and show enhanced degradation via the proteasome, resulting in apoptosis. In PERK knockdown cells, SubAB-induced loss of ubiquitinated proteins was inhibited. Thus, SubAB-induced ER stress is caused by BiP cleavage, leading to PERK activation, not by accumulation of ubiquitinated proteins, which undergo PERK-dependent degradation via the ubiquitin-proteasome system.

scholarly journals HPV Oncoproteins and the Ubiquitin Proteasome System: A Signature of Malignancy?

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 133 ◽  
Author(s):  
Anamaria Đukić ◽  
Lucija Lulić ◽  
Miranda Thomas ◽  
Josipa Skelin ◽  
Nathaniel Edward Bennett Saidu ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Cellular Functions ◽  
Hpv E6 ◽  
System A ◽  
Ubiquitin Proteasome ◽  
Cellular Pathways ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7 ◽  
Hpv Oncoproteins ◽  
Regulation Of Cell Cycle

Human papillomavirus (HPV) E6 and E7 oncoproteins are critical for development and maintenance of the malignant phenotype in HPV-induced cancers. These two viral oncoproteins interfere with a plethora of cellular pathways, including the regulation of cell cycle and the control of apoptosis, which are critical in maintaining normal cellular functions. E6 and E7 bind directly with certain components of the Ubiquitin Proteasome System (UPS), enabling them to manipulate a number of important cellular pathways. These activities are the means by which HPV establishes an environment supporting the normal viral life cycle, however in some instances they can also lead to the development of malignancy. In this review, we have discussed how E6 and E7 oncoproteins from alpha and beta HPV types interact with the components of the UPS, and how this interplay contributes to the development of cancer.

scholarly journals Mapping the interactome of HPV E6 and E7 oncoproteins with the ubiquitin-proteasome system

FEBS Journal ◽  
2017 ◽  
Vol 284 (19) ◽  
pp. 3171-3201 ◽  
Author(s):  
Juline Poirson ◽  
Elise Biquand ◽  
Marie-Laure Straub ◽  
Patricia Cassonnet ◽  
Yves Nominé ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Hpv E6 ◽  
Ubiquitin Proteasome ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

The ubiquitin–proteasome system and skeletal muscle wasting

2005 ◽  
Vol 41 ◽  
pp. 173-186 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Proteolytic Enzymes ◽  
Cathepsin L ◽  
Ubiquitin Proteasome System ◽  
Complete Breakdown ◽  
Skeletal Muscle Proteins ◽  
Ubiquitin Proteasome ◽  
Tripeptidyl Peptidase Ii ◽  
F Box Protein

The ubiquitin–proteasome system (UPS) is believed to degrade the major contractile skeletal muscle proteins and plays a major role in muscle wasting. Different and multiple events in the ubiquitination, deubiquitination and proteolytic machineries are responsible for the activation of the system and subsequent muscle wasting. However, other proteolytic enzymes act upstream (possibly m-calpain, cathepsin L, and/or caspase 3) and downstream (tripeptidyl-peptidase II and aminopeptidases) of the UPS, for the complete breakdown of the myofibrillar proteins into free amino acids. Recent studies have identified a few critical proteins that seem necessary for muscle wasting {i.e. the MAFbx (muscle atrophy F-box protein, also called atrogin-1) and MuRF-1 [muscle-specific RING (really interesting new gene) finger 1] ubiquitin–protein ligases}. The characterization of their signalling pathways is leading to new pharmacological approaches that can be useful to block or partially prevent muscle wasting in human patients.

The ubiquitin–proteasome system and skeletal muscle wasting

2005 ◽  
Vol 41 (1) ◽  
pp. 173 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Ubiquitin Proteasome System ◽  
Skeletal Muscle Wasting ◽  
Ubiquitin Proteasome

Theoretical Studies of the Acid-Base Equilibria in a Model Active Site of the Human 20S Proteasome

2020 ◽  
Author(s):  
Jon Uranga ◽  
Lukas Hasecke ◽  
Jonny Proppe ◽  
Jan Fingerhut ◽  
Ricardo A. Mata
Keyword(s):  
Active Site ◽  
Boronic Acid ◽  
Computational Study ◽  
Ubiquitin Proteasome System ◽  
Bayesian Optimization ◽  
Inhibition Mechanism ◽  
20S Proteasome ◽  
Acid Base ◽  
Ubiquitin Proteasome ◽  
Infection Cycles

The 20S Proteasome is a macromolecule responsible for the chemical step in the ubiquitin-proteasome system of degrading unnecessary and unused proteins of the cell. It plays a central role both in the rapid growth of cancer cells as well as in viral infection cycles. Herein, we present a computational study of the acid-base equilibria in an active site of the human proteasome, an aspect which is often neglected despite the crucial role protons play in the catalysis. As example substrates, we take the inhibition by epoxy and boronic acid containing warheads. We have combined cluster quantum mechanical calculations, replica exchange molecular dynamics and Bayesian optimization of non-bonded potential terms in the inhibitors. In relation to the latter, we propose an easily scalable approach to the reevaluation of non-bonded potentials making use of QM/MM dynamics information. Our results show that coupled acid-base equilibria need to be considered when modeling the inhibition mechanism. The coupling between a neighboring lysine and the reacting threonine is not affected by the presence of the inhibitor.

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